Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans

Abstract

Aims: In humans, impaired gastric accommodation is associated with early satiety and weight loss. In animals, accommodation involves activation of gastric nitrergic neurones. Our aim was to study involvement of nitric oxide in gastric accommodation and in meal induced satiety in humans. Methods: The effect of N G -monomethyl-L-arginine (L-NMMA) 4 mg/kg/h and 8 mg/kg/h on gastric compliance, on sensitivity to distension, and on gastric accommodation was studied with a barostat in double blind, randomised, placebo controlled studies. The effect of L-NMMA 8 mg/kg/h on meal induced satiety was studied using a drinking test. Results: L-NMMA had no significant effect on fasting compliance and sensitivity. Ingestion of a meal induced a relaxation of 274 (15) ml which was significantly smaller after L-NMMA 4 mg/kg/h (132 (45) ml; p=0.03) or L-NMMA 8 mg/kg/h (82 (72) ml; p=0.03). L-NMMA 8 mg/kg/h significantly decreased the amount of food ingested at maximum satiety from 1058 (67) to 892 (73) kcal (p<0.01). Conclusion: In humans, fasting gastric tone and sensitivity to distension are not influenced by nitric oxide synthase inhibition, but the gastric accommodation reflex involves activation of nitrergic neurones. Inhibition of nitric oxide synthase impairs accommodation and enhances meal induced satiety.

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

“…Postprandial accommodation is primarily attributed to nutrient-driven stimulation of vagal activity, which activates enteric nitrergic pathways to relax the stomach (9,23,27,43). Thus L-NMMA blunted postprandial accommodation in healthy subjects (26,42). Several previous studies have demonstrated that GLP-1 administered at doses comparable or lower to those given in this study inhibited vagal activity, thereby inhibiting gastric antral motility and acid secretion in humans (8,39).…”

“…L-NMMA (Clinalfa, Läufelfingen, Switzerland), a NOS inhibitor, was infused at 4 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 . In healthy subjects, this dose stimulated small intestinal motility (38) and reduced postprandial accommodation (42).…”

Lack of Modulation of Gastric Emptying by Dietary Nitrate in Healthy Volunteers

“…The gastric emptying process is a complex interplay between the proximal fundus and the distal antrum (Minami and McCallum 1984), probably making it difficult to identify potential influence by nitrate administration using total gastric emptying as a parameter in this study. Other than the gastric emptying, NO is also involved in other gastric motor functions such as basal fundic tone and fundic relaxation, which is an important function for the accommodation after food (Tack et al 2002;Kuiken et al 2002). Considering that NO generation within the stomach following nitrate ingestion occurs predominantly in the proximal fundus (Iijima et al 2002), these parameters associated directly with the fundic function might have been more suitable for evaluating the effect of dietary nitrate on gastric motor function.…”

Effect of pancreatic polypeptide on gastric accommodation and gastric emptying in conscious rats

“…The stomach is known to relax upon food intake. This reflex relaxation, also referred to as gastric accommodation (GA), enables the stomach to receive large quantities of food without an increase in intragastric pressure (IGP) (35). Relaxation of the stomach upon food intake is mediated via vago-vagal reflex pathways, eventually leading to activation of mainly nitrergic nerves in the enteric nervous system (38).…”